Potential mechanisms of Bifidobacterium-mediated synergistic antibiotic eradication of drug-resistant Helicobacter pylori

The rising prevalence of antibiotic-resistant Helicobacter pylori has become a major obstacle to the success of conventional eradication therapies, including triple and quadruple regimens combining antibiotics with proton pump inhibitors. There is an urgent need for safe and effective ad-junctive strategies to restore antibiotic efficacy. Probiotics, particularly Bifidobacterium species, have gained increasing attention for their potential to enhance H. pylori eradication and mitigate treatment-associated adverse effects. This review provides a comprehensive synthesis of the key molecular mechanisms driving H. pylori antibiotic resistance, including chromosomal mutations, altered expression of outer membrane proteins, enhanced efflux pump activity, biofilm formation, and morphological transition into dormant coccoid forms. Importantly, we critically examine the emerging evidence on how Bifidobacterium may synergize with antibiotics to counteract these resistance mechanisms. The proposed mechanisms include the secretion of bioactive metabolites (e.g., organic acids and antimicrobial peptides), reinforcement of the gastric mucosal barrier, modulation of host immune responses, and competitive exclusion of H. pylori . By integrating these mechanistic in-sights, this review highlights the potential of Bifidobacterium as a promising adjunctive therapeutic agent for overcoming antibiotic-resistant H. pylori infections and calls for more rigorous, strain-specific clinical investigations to translate these findings into practice.